Abstract

Human herpesvirus (HHV) 6 causes substantial morbidity and mortality in the immunocompromised host and has no approved therapy. Adoptive transfer of virus specific T cells has proven safe and apparently effective as prophylaxis and treatment of other virus infections in immunocompromised patients; however, extension to subjects with HHV6 has been hindered by the paucity of information on targets of cellular immunity. We now characterize the cellular immune response from 20 donors against five major HHV6B antigens predicted to be immunogenic and define a hierarchy of immunodominance of antigens based on the frequency of responding donors and the magnitude of the T cell response. We identified specific epitopes within these antigens and expanded the HHV6 reactive T cells using a GMP-compliant protocol. The expanded population comprised both CD4+ and CD8+ T cells that were able to produce multiple effector cytokines and kill both peptide-loaded and HHV6B wild type virus-infected target cells. Thus, we conclude that adoptive T cell immunotherapy for HHV6 is a practical objective, and that the peptide and epitope tools we describe will allow such cells to be prepared, administered and monitored in human subjects.